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Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the fibrillin-1 gene. Acute aortic dissection is the leading cause of death in patients suffering from MFS and consequence of medial degeneration and aneurysm formation. In addition to its structural function in the formation of elastic fibers, fibrillin has a major role in keeping maintaining transforming growth factor ß (TGF-ß) in an inactive form. Dysfunctional fibrillin increases TGF-ß bioavailability and concentration in the extracellular matrix, leading to activation of proinflammatory transcription factors. In turn, these events cause increased expression of matrix metalloproteinases and cytokines that control the migration and infiltration of inflammatory cells into the aorta. Moreover, TGF-ß causes accumulation of reactive oxygen species leading to further degradation of elastin fibers. All these processes result in medial elastolysis, which increases the risk of vascular complications. Although MFS is a hereditary disease, symptoms and traits are usually not noticeable at birth. During childhood or adolescence affected individuals present with severe tissue weaknesses, especially in the aorta, heart, eyes, and skeleton. Considering this, even young patients should avoid activities that exert additional stress and pressure on the aorta and the cardiovascular system. Thus, if the diagnosis is made and prophylactic treatment is initiated in a timely fashion, MFS and its preliminary pathophysiologic vascular remodeling can be successfully ameliorated reducing the risk of life-threatening complications. This commentary focuses on new research opportunities and molecular findings on MFS, discusses future challenges and possible long-term therapies.

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The current study describes the results obtained from clinical examination of over 4700 suckling piglets from 19 individual herds in Germany. In this cohort the prevalence of inflammation and necrosis in the tails, ears, claw coronary bands, heels and teats was determined using a pre-defined scoring system. Results show that already in the 1st days of life, piglets were affected by inflammation and necrosis of the heels (80%), claw coronary bands (50%) and tail base (20%). The praevalences of these alterations in piglets were influenced by genetics (P <0.001) and age, decreasing gradually in the 2nd week of life (P <0.001). Moreover, a correlation between tail length after tail docking and the prevalence of tail necrosis (P⩽0.04) was found. Tail and ear biting as a behavioural trait was not detected during this study. The early onset, appearance and multiple locations of clinical signs of inflammation and the positive correlation with the genetic background of the piglets may suggest an impairment of the innate immune system by infectious and non-infectious agents. This is in contrast to previously described behavioural abnormalities seen in fattening pigs. Considering the obvious reduction of animal welfare due to the described lesions, there is a need to create awareness among pig farmers and to understand the multifactorial causality involved in this inflammation and necrosis syndrome in piglets.

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OBJECTIVE: Retrograde aortic type A dissection (RTAD) is a known complication in patients with aortic type B dissection. The purpose of this computational fluid dynamics (CFD) study was to identify haemodynamic risk factors for the occurrence of RTAD. METHODS: Computed tomographic angiography (CTA) images of 10 patients with type B dissections, who subsequently developed a RTAD, were retrospectively analysed together with patients constituting a control group (n = 10) where no further vascular events after the initial type B dissection occurred. CFD simulations were conducted based on 3D surface models of the aortic lumen derived from CTA datasets. For both groups, pressures, velocity magnitudes and wall shear stress (WSS) were compared at the site of the future RTAD entry tear and the surrounding aortic wall. RESULTS: WSS at the site of the future entry tear was significantly elevated compared with the surrounding wall (15.10 Pa vs. 5.15 Pa, p < .001) and was significantly higher in the RTAD group than in the control group (6.05 Pa, p < .002). Pressures and velocity magnitudes were not significantly elevated at the entry tear (3825.8 Pa, 0.63 m/s) compared with the aortic arch (3549.8 Pa, 0.50 m/s) or control group (3501.7 Pa, 0.62 m/s). CONCLUSIONS: Increased WSS accompanies the occurrence of RTAD. The results merit the design for a prospective study to confirm whether WSS is a risk factor for the occurrence of RTAD.

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BACKGROUND: Chronic nonhealing or recurrent inflammatory lesions, reminiscent of infection but recalcitrant to antibiotic therapy, generally characterize biofilm-driven diseases. Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well-known biofilm infections. OBJECTIVES: To determine and quantify the potential presence of bacterial aggregates in chronic HS lesions. METHODS: In 42 consecutive patients with HS suffering from chronic lesions, biopsies were obtained from lesional as well as from perilesional skin. Samples were investigated using peptide nucleic acid-fluorescence in situ hybridization in combination with confocal laser scanning microscopy. In addition, corresponding histopathological analysis on haematoxylin and eosin slides was performed. RESULTS: Biofilms were seen in 67% of the samples of chronic lesions and in 75% of the perilesional samples. The mean diameter of aggregates in lesional skin was significantly greater than in perilesional skin (P = 0·01). Large biofilms (aggregates > 50 µm in diameter) were found in 42% of lesional samples and in only 5% of the perilesional samples (P = 0·009). The majority of the large biofilms were situated in sinus tracts (63%) or in the infundibulum (37%). The majority of the sinus tract samples (73%) contained active bacterial cells, which were associated with inflammation. CONCLUSIONS: This study suggests that biofilm formation is associated with inflammation of chronic HS lesions. The aggregates most likely occur as a secondary event, possibly due to predisposing local anatomical changes such as sinus tracts (tunnels), keratinous detritus and dilated hair follicles.

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BACKGROUND: Genetic aortic syndromes are autosomal-dominantly heritable aneurysms of the thoracic aorta, which carry a high risk of aortic rupture or acute thoracic aortic dissection at young age. OBJECTIVES: We introduce the reader to the principles of genetic diagnostics and the medical and surgical prevention of thoracic aortic dissection in patients with genetic aortic syndromes. METHODS: A cardiologist, a health economist, a patient representative, a heart surgeon, and a molecular geneticist teamed up to elucidate their perspective on major aspects of genetics and prevention of genetic aortic syndromes. RESULTS: Genetic aortic syndromes reflect a broad spectrum of diverse disease entities comprising the Marfan syndrome, the Loeys-Dietz syndrome or the vascular Ehlers-Danlos syndrome. The diagnosis of each respective disease entity requires combined assessment of phenotype and genotype information. A medical prevention of aortic complications such as dissection is mandatory although a curative therapy currently appears unlikely in humans. The single most important measure against acute aortic dissection is the preventive replacement of the aortic root, where valve preserving techniques appear preferable. Comprehensive prophylaxis including molecular diagnostics seem reasonable also from an economic point of view. DISCUSSION: Optimal prevention requires individualization of concepts, which entail a detailed diagnostic characterization of each specific genetic aortic syndrome including characterization of the genotype.

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BACKGROUND: The working group "Aortic Surgery and Interventional Vascular Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) set up the German registry for acute aortic dissection type A (GERAADA) in July 2006. This web-based database was developed to record data of patients who had undergone surgery for aortic dissection type A (AADA). The aim of GERAADA is to learn from analyzing the data of AADA patients how to improve the perioperative management and surgical treatment of patients with AADA and to identify possible parameters affecting patient risk and outcome. PATIENTS AND METHODS: Between July 2006 and June 2009 (2010), 1558 (2137) patients with AADA were enrolled in the multi-center, prospective GERAADA database by 50 cardiac surgery centers in German-speaking countries in Europe. Data on patients' preoperative and intraoperative status, postoperative complications, midterm results and circumstances of death were recorded. Data were analyzed to identify risk factors influencing the outcome of these patients. The Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) in Mainz performed the statistical analyses. RESULTS: Analyses from GERAADA reveal a thirty-day mortality of 17% in 2137 AADA patients. Only short interventions in aortic arch surgery are safe during hypothermic circulatory arrest even without selective cerebral perfusion. If circulatory arrest times of over 30 min. are anticipated, antegrade cerebral perfusion is strongly recommended during the entire arch intervention using cardiopulmonary bypass. Surgical strategy in terms of isolated ascending aortic replacement versus ascending aortic replacement combined with aortic arch repair had no statistical relevant influence on 30-day mortality. AADA surgical results in elderly patients are more encouraging than those treated without surgery. Surgery is even feasible in octogenarians with a 35% mortality rate. CONCLUSION: The aim of this registry is to optimize AADA patients' medical care, thereby reducing their morbidity and mortality. AADA treatment should always involve open surgery. Initial analyses from GERAADA provide clinically relevant insights concerning patients with AADA, and may enable therapeutic recommendations for improving perioperative and surgical management. Our latest study detected significant influencing risk factors for the outcome of AADA patients and may contribute to a consensus in setting guidelines for standard medical treatment. PERSPECTIVE: A European Registry of Aortic Diseases ("EuRADa") is being established this year under the leadership of the "Vascular Domain" of the European Association for Cardio-Thoracic Surgery (EACTS). This database will collect parameters on all aortic diseases, dissection types A and B, aneurysms, perforating ulcer (PAU), intramural wall hematoma (IMH), traumatic aortic ruptures, and all potential treatment strategies (medical treatment, open surgical and endovascular).

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Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000 births, leading to a fibrillin connective tissue disorder with manifestations in the skeleton, eye, skin, dura mater and in particular the cardiovascular system. Since other syndromes demonstrate similar vascular manifestations, but therapy may differ significantly, diagnosis should be established using the revised Ghent nosology in combination with genotypic analysis in specialized Marfan centres. The formation of aortic root aneurysms with the subsequent risk of acute aortic dissection type A (AADA) or aortic rupture limits life expectancy in patients with Marfan syndrome. Therefore, prophylactic replacement of the aortic root needs to be performed before the catastrophic event of AADA can occur. The goal of surgery is the complete resection of pathological aortic tissue. This can be achieved with excellent results by using a (mechanically) valved conduit that replaces both the aortic valve and the aortic root (Bentall operation). However, the need for lifelong anticoagulation with Coumadin can be avoided using the aortic valve sparing reimplantation technique according to David. The long-term durability of the reconstructed valve is favourable, and further technical improvements may improve longevity. Although results of prospective randomised long-term studies comparing surgical techniques are lacking, the David operation has become the surgical method of choice for aortic root aneurysms, not only at the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch is performed under moderate hypothermic circulatory arrest combined with antegrade cerebral perfusion using a heart-lung machine, which we also use in thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a Marfan centre is pivotal for the early detection of pathological changes on the diseased aorta.

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OBJECTIVE: We wanted to investigate if retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) might be a good marker of acute and chronic changes in the afferent visual pathway following acute optic neuritis (ON). METHODS: We studied the relationship of optic nerve lesion length, optic nerve mean area, and RNFLT, quantified by OCT, with fMRI response to a visual paradigm in 40 patients with acute ON and 19 healthy controls in a prospective cohort study over a 6-month period. RESULTS: The main finding was a significant correlation of optic nerve lesion length and mean area with fMRI response in affected eyes in the acute phase and between RNFLT and fMRI response in affected eyes after recovery. CONCLUSION: RNFLT is a very good measure of damage to the afferent visual pathway in recovered patients with ON and should be included in future fMRI studies when looking for visual reorganization in recovered patients with ON.

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BACKGROUND: The working group for aortic surgery and interventional vascular surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) initiated the web-based German Registry for Acute Aortic Dissection type A (GERAADA). It is the project's aim to collect standardized data from a large pool of patients with acute aortic dissections type A (AADA) to gain a deeper insight and knowledge to improve surgical therapies and perioperative management for these patients in the future. METHODS: In addition to new medical insights, the working group has gained more experience over the last 4 years in how to collect valid and high-quality data. This experience led us to revise the database completely. In this article we describe the new version of GERAADA, providing an overview as well as defining the parameters, and explaining the new features. This overview fulfills a request by the users of GERAADA in the participating centers. RESULTS: Since its inception, 50 cardiac centers in Germany, Austria and Switzerland have provided over 2000 records and the first statistical results have been published. CONCLUSION: GERAADA's new design allows it to stay abreast of changes in medicine and to focus on the essentials necessary for statistically relevant results, while keeping the work load low for the data providers at each cardiac center.

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A German registry for acute aortic dissection type A (GERAADA) was initiated by the Working Group for Aortic Surgery and Interventional Vascular Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in July 2006. This web-based database was developed to record the data of patients who had undergone surgery for aortic dissection type A. From analyzing the data, we aim to learn how to improve surgical treatment and to identify parameters affecting patient outcome. In the beginning, 33 cardiac centers participated via online access to the registry on the GSTCVS' homepage. Since then, 43 centers in Germany, Switzerland and Austria have begun entering data on the pre- and intraoperative status of their patients, postoperative complications, mid-term results and circumstances of death. We have succeeded in interpreting the initial results and trends from the registry now available to all of the participating centers, which benefit from this shared pool of analyzed data by optimizing their therapy regimes and comparing their success with that in the other centers.

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BACKGROUND: Acute optic neuritis occurs with and without papillitis. The presence of papillitis has previously been thought to imply an anterior location of the neuritis, but imaging studies seeking to test this hypothesis have been inconclusive. METHODS: This prospective observational cohort study included 41 patients with unilateral optic neuritis and 19 healthy volunteers. All patients were evaluated and examined within 28 days of onset of symptoms. The peripapillary retinal nerve fiber layer thickness (RNFLT), an objective quantitative measure of optic nerve head edema, was measured by optical coherence tomography and the length and location of the inflammatory optic nerve lesion were evaluated using MRI. RESULTS: Ophthalmoscopically, 34% of the patients had papillitis. The retinal nerve fiber layer in affected eyes (mean 123.1 microm) was higher during the acute phase than that of fellow eyes (mean 98.1 microm, p < 0.0001) and higher than that in healthy control eyes (mean 97.1 microm, p < 0.0001). The RNFLT was related to the length of the optic nerve lesion (p = 0.0002), but not to the location of the optic nerve lesions (p = 0.72). CONCLUSIONS: In this study of the acute phase of optic neuritis, the degree of optic nerve head edema depended upon the extent of the optic nerve lesion, but not on its location. This suggests that factors other than inflammation, such as compromised venous drainage, vascular leakage, impaired axonal transport, and other mechanisms, are involved in the development of optic nerve head edema in optic neuritis.

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OBJECTIVE: To confirm the quality of total arterial CABG carried out using the left internal thoracic artery (LITA) and a radial artery (RA) T-graft and distal anastomoses immediately in the OR, we developed a new technique using intraoperative graft angiography. METHODS: A 5-Fr sheath is inserted in the proximal radial artery stump, through which a catheter for LITA angiography is later introduced. From July 2004 to March 2005, 23 patients underwent total arterial CABG with the T-graft and intraoperative graft angiography. RESULTS: On-pump CABG was performed in 22 patients and off-pump CABG in 1 patient. Mean procedure time for the angiography was 13.7 +/- 7.3 minutes, and mean fluoroscopy time was 6.2 +/- 4.6 minutes. In two patients, the RA-marginal artery side-to-side anastomosis was stenosed and had to be revised as demonstrated by graft angiography. In one patient, the RA was kinked and in another, there was a kinking of the LITA. In both cases, kinking was corrected. The remaining anastomoses were seen to have unobstructed flow with no evidence of stenosis. CONCLUSIONS: Intraoperative graft angiography can be performed in patients undergoing total arterial CABG. This concept of intraoperative cooperation between an interventional cardiologist and surgeons could significantly improve the operative outcome in CABG surgery.

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Optical coherence tomography (OCT) is a new noninvasive high-resolution method that measures the retinal nerve fiber layer (RNFL) thickness. An overview of the use in optic neuritis (ON) and multiple sclerosis (MS) is presented. Literature survey of PubMed was carried out. RNFL thickness in eyes of healthy control subjects was 102.9-111.11 microm, in eyes affected by ON 59.79-85 microm, and in fellow eyes 82.73-99.8 microm. All studies found a significant reduction in RNFL in eyes affected by ON compared with fellow eyes and eyes of healthy controls. Two out of three studies found a significant reduction in RNFL in fellow eyes compared with control eyes. RNFL thickness correlated with visual acuity, visual field, low-contrast letter acuity, contrast sensitivity, and color vision. Correlations were also found with the optic nerve area evaluated by magnetic resonance imaging, neurologic impairment score, and increasing disease duration. One of two studies found a significant correlation with amplitudes of visual evoked potentials, neither correlated with latencies. OCT is a promising new tool for evaluating atrophy in patients with ON and MS.

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AIMS: The significant shortage of donor organs in lung transplantation necessitates a careful selection of lung transplant recipients. The outcome of lung transplant recipients aged 60 years and older has not been analyzed systematically. METHODS: We retrospectively reviewed our experience with older recipients. Between January 1999 and July 2003, 248 patients underwent lung transplantation at our institution, of which 18 were aged 60 years and older (7.3%, range 60-66, mean 62 +/- 1.1). RESULTS: Eleven (61%) of the recipients 60 years and older received a single (SLTx) and seven (39%), a bilateral lung transplant. Donor age in the single transplant cohort was 30 +/- 4 years. It was 33 +/- 3 years in bilateral patients. Posttransplant ventilation time was significantly different among groups, with 282 +/- 32 hours after bilateral and 56 +/- 13 hours after transplant (P < .05). Also significantly longer was the length of the ICU stay in the bilateral group. First PaO2 in the ICU was not different among the two groups. The 1-year survival in the single transplant group was significantly better compared to the bilateral group with 73% versus 43%, respectively. CONCLUSIONS: The 1-year survival following lung transplantation in patients older than 60 years is markedly reduced compared to recipients under 60 years of age. If a lung transplant is considered in a recipient above the age of 60 years, a single transplant should be favoured. If that is not indicated, patients over 60 should be very carefully selected for bilateral transplant.

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OBJECTIVES: To prove whether different indications for valve sparing aortic root reconstruction may have an impact on the outcome and longevity of the repair. METHODS: From July 1993 to March 2003, the reimplantation technique for valve sparing aortic root reconstruction was applied to 232 patients. In 44 patients, indication for operation was acute aortic dissection type A (AADA). These patients were compared with 44 randomised patients operated for aortic root aneurysm (root) by matched pair analysis with respect to age, gender, time point of operation and presence of Marfan's syndrome. Peri- and post-operative courses with focus on survival and valvular stability were analysed. RESULTS: Pre-operative grade of aortic insufficiency was 2.4+/-1 in root vs. 1.5+/-1.7 in AADA (P = 0.004) Mean CPB-time (214+/-60 vs. 171+/-42 min;P < 0.001), aortic cross clamp time (158+/-40 vs. 129+/-39 min; P = 0.001) and stay on ICU (5.2+/-9 vs. 1.7+/-1 days; P = 0.034) were longer for AADA, while hospitalisation was comparable (14+/-10 vs. 14+/-7 days; P = 0.88). Five patients (11.4%) from AADA died peri-operatively compared to no patient from root (P = 0.055). None of the early deaths were valve-related. Re-thoracotomy rate was 6.8% for both groups. Mean follow-up was 19+/-21 months for AADA vs. 28+/-21 months for root (P = 0.038) Survival at 3 years was 88+/-5% for AADA and 100% for root (P = 0.028). Freedom from valvular reoperation was 97+/-2.7% for root and 97+/-3% for AADA at 3 years (P = 0.44). At last investigation, mean grade of aortic insufficiency for AADA was 0.2+/-0.3 compared to 0.3+/-0.3 for root (P = 0.34) CONCLUSIONS: Regardless of the underlying indication, the aortic valve preserving reimplantation technique can be performed with favourable functional results.

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OBJECTIVE: Acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. However, there is concern about the possibility of porcine endogenous retrovirus transmission. In this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. METHODS: Acellularized porcine pulmonary valve conduits (n = 3) and in vitro autologous repopulated porcine pulmonary valve conduits (n = 5) were implanted into sheep in the pulmonary valve position. Surgery was carried out with cardiopulmonary bypass support. The animals were killed 6 months after the operation. Blood samples were collected regularly up to 6 months after the operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, explanted tissue-engineered heart valves were tested for porcine endogenous retrovirus after 6 month in vivo. RESULTS: Porcine endogenous retrovirus DNA was detectable in acellularized porcine heart valve tissue. However, 6 months after implantation of in vitro and in vivo repopulated acellularized porcine heart valve scaffolds, no porcine endogenous retrovirus sequences were detectable in heart valve tissue and peripheral blood. CONCLUSION: Acellularized porcine matrix scaffolds used for creation of tissue-engineered heart valves do not transmit porcine endogenous retrovirus.

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BACKGROUND: Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation. METHODS AND RESULTS: From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43+/-26 months, group B 40+/-25 months, group C 23+/-19 months; group C versus group A, P=0.005; group C versus group B, P=0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%; P=ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98+/-2%, for group B 96+/-3%, and for group C 100+/-0% (P=ns). Freedom from reoperation for group A was 98+/-2%, for group B 96+/-3%, and for group C 88+/-8% (P=ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100+/-0%, for group B 88+/-8%, and for group C 94+/-5% (P=ns). During follow-up no thromboembolic or bleeding events were noticed. CONCLUSIONS: Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.

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OBJECTIVE: Acute dissection of the ascending aorta requires immediate surgical intervention. In this study, we report our first results with valve sparing aortic root reconstruction removing all the diseased tissues. METHODS: From August 1995 to December 2000, 22 patients with acute aortic dissection of the ascending aorta (Stanford type A) underwent valve sparing aortic root reconstruction. Their ages ranged from 20 to 76 years (52+/-15, 68% males). Dissection was found in the ascending aorta (3 patients) or both in the ascending aorta and aortic arch (19 patients; 86%). Course and length of hospitalization, echocardiographic and clinical follow-up, complications and mortality were analysed. RESULTS: Mean cardiopulmonary bypass time was 212+/-56 min (134-352 min), mean aortic cross clamp time was 157+/-24 min (114-205 min). In patients undergoing additional arch replacement (n=19), circulatory arrest was 35+/-18 min (11-75 min). After reconstruction, intraoperative echocardiography showed aortic insufficiency (AI) grade 0 in 16 patients (84%) and grade 1 in three patients (16%). Stay in intensive care unit was 2.1+/-0.7 days, and postoperative hospitalization was 21+/-14.4 days. There were three perioperative deaths (14%). Mean post-operative follow-up was 18.4+/-18 months (0.4-65.4 month). One patient died 10 months postoperatively. At follow-up, no patient suffered AI grade 2 or higher, and no reoperation for aortic valve failure was necessary. All patients presented with a favorable exercise tolerance being in New York Heart Association functional class I or II. CONCLUSION: Valve sparing aortic root reconstruction in patients with type A dissection can be performed with acceptable intraoperative mortality and morbidity and excellent results during follow-up. The complete resection of the diseased aorta is particularly appealing.

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